Studies On The Preparations And Properties Of Polyelectrolyte Complex Nanoparticles

Polyelectrolyte complex micelles as drug carriers have a bright prospect in cancertherapy. The prodrugs formed through complexation of charged drugs and polyelectrolytepolymer has many advantages such as high drug loading efficiency, stable loading andcontrollable release behaviors. They can potentially be used as drug vehicles.In the present work, firstly, the ionomer of Poly(MA-co-LA)-b-PEG was prepared by adirect polycondensation of D,L-lactic acid(LA), L-malic acid(MA) and monomethylpolyethylene glycol (PEG) using stannous chloride (SnCl2) as the catalyst. Through changingthe components of MA and LA, a series of random ionomers were prepared. The structure andthermal stability of ionomers were confirmed by FT-IR,1H-NMR, GPC, TGA, and DSC. Bychoosing doxorubicin as a model, a polyion complex (PIC) nano prodrug based on thecomplexation of doxorubicin (DOX) with the ionomers of poly(lactic acid-co-malic acid)-block-polyethylene glycol [Poly(MA-co-LA)-b-PEG] was developed. The ionomer couldcomplex with doxorubicin (DOX) using side carboxyl groups of MA units and amino groupsof DOX. It was observed that the loading efficiency of DOX reached up to as high as18.2%.The strucure and properties of the nanoparticles were extensively characterized and studied.The results show that they have stable core-shell structure, regular morphology and the diameteris about150nm. The anticancer drug (doxorubicin) was released in different saline solutions.The release profiles revealed that the drug release could be controlled by adjusting the pH andsalt concentrations.In order to enhance the stability of the main chains, the ionomer of Poly(LA-co-GA)-b-mPEG was prepared by a direct polycondensation of D,L-lactic acid(LA), L-glutamic acid(GA) and mPEG by one-step. The polyester and polyamide bonds were involved at same timein the main chains of the ionomer. Different ionomers were prepared by changing the molarratio of LA and GA in feeds. The structure of the ionomers were proved by FT-IR, TGA andelemental analysis. The results showed that the target products were successfully synthesized.The nanoparticles with molar ratio of GA: LA: mPEG=1:0.5:0.5(GLP-0.5) possess sphericalmorphology with an average diameter of120nm in narrow distribution. The nanoparticleswere non-toxic and still very stable after stored for one month at37oC, which was essential fortheir application as drug carriers. The drug loading and embedding rate of GLPD-0.5toward doxorubicin reached up to17.5%and76%respectively. The release profile demonstrated pHsensitivity and apparent slow-releasing effect.The nanoparticles displayed apparent advantages such as simple preparation process, lowcost, being free of organic solvents, drug as a group of the nanoparticles, good biodegradableand biocompatible.